crossing96/oncoscreening huggingface dataset:
Effectiveness of Adjuvant Chemotherapy for Locally Advanced Bladder Cancer.	PURPOSE: Given that randomized trials exploring adjuvant chemotherapy for bladder cancer have been underpowered and/or terminated prematurely, yielding inconsistent results and creating an evidence gap, we sought to compare the effectiveness of cystectomy versus cystectomy plus adjuvant chemotherapy in real-world patients. PATIENTS AND METHODS: We conducted an observational study to compare the effectiveness of adjuvant chemotherapy versus observation postcystectomy in patients with pathologic T3-4 and/or pathologic node-positive bladder cancer using the National Cancer Data Base. We compared overall survival using propensity score (-adjusted, -stratified, -weighted, and -matched) analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to examine the impact of performance status. RESULTS: A total of 5,653 patients met study inclusion criteria; 23% received adjuvant chemotherapy postcystectomy. Chemotherapy-treated patients were younger and more likely to have private insurance, live in areas with a higher median income and higher percentage of high school-educated residents, and have lymph node involvement and positive surgical margins (P < .05 for all comparisons). Stratified analyses adjusted for propensity score demonstrated an improvement in overall survival with adjuvant chemotherapy (hazard ratio, 0.70; 95% CI, 0.64 to 0.76), and similar results were achieved with propensity score matching and weighting. The association between adjuvant chemotherapy and improved survival was consistent in subset analyses and was robust to the effects of poor performance status. CONCLUSION: In this observational study, adjuvant chemotherapy was associated with improved survival in patients with locally advanced bladder cancer. Although neoadjuvant chemotherapy remains the preferred approach based on level I evidence, these data lend further support for the use of adjuvant chemotherapy in patients with locally advanced bladder cancer postcystectomy who did not receive chemotherapy preoperatively.	bladder
Chemotherapy for Muscle-Invasive Bladder Cancer: Better Late Than Never?	The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 64-year-old man with a history of cigarette smoking but no significant comorbidities presented with hematuria and dysuria. Computed tomography scans demonstrated a mass and thickening of the bladder wall and no evidence of metastasis. His laboratory evaluation showed normal blood cell counts and comprehensive metabolic panel with a calculated creatinine clearance of more than 60 mL per minute. A transurethral resection of the bladder tumor and biopsy identified transitional cell carcinoma or urothelial carcinoma invading the muscularis propria of the bladder. On the basis of the bladder-confined mass on computed tomography scan, the tumor was assigned a clinical stage of cT2N0. The patient was advised to undergo neoadjuvant chemotherapy followed by radical cystectomy (RC). The patient had multiple concerns regarding neoadjuvant chemotherapy, particularly toxicities, especially the possibility of chronic neurologic and renal toxicities, and the potential harm from delay of RC, especially if the bladder cancer was resistant to chemotherapy. After a discussion of approximately 1 hour, he elected to proceed with upfront RC and extended lymph node dissection in conjunction with construction of a neobladder. Pathology revealed pathologic extravesical urothelial carcinoma, with disease in one of 25 lymph nodes removed (ypT3N1). Four weeks after RC, he returned to discuss further management with the medical oncologist. He exhibited an Eastern Cooperative Oncology Group performance status of 0, normal blood cell counts, and a calculated creatinine clearance of more than 60 mL per minute.	bladder
Lymphovascular invasion status at transurethral resection of bladder tumors may predict subsequent poor response of T1 tumors to bacillus Calmette-Guérin.	BACKGROUND: Lymphovascular invasion (LVI) is an important step in the process of tumor dissemination and metastasis outside the primary organ, but the relationship between LVI and the prognosis of T1 non-muscle invasive bladder cancer (NMIBC) has not been fully evaluated. Accordingly, the present study was performed to evaluate whether LVI had an impact on the clinical outcome in patients with T1 NMIBC. METHODS: A total of 116 consecutive patients were diagnosed with T1 NMIBC from 1994 to 2013 at Keio University Hospital. All cases were reviewed by a single uro-pathologist. The prognostic significance of LVI was assessed in relation to recurrence and stage progression. RESULTS: The median follow-up period was 53 months. LVI was histologically confirmed in 30 patients (25.9%). There were no significant differences of clinical features between the patients with and without LVI. In T1 patients, univariate analysis demonstrated that LVI positivity was associated with stage progression (p = 0.003), but not with tumor recurrence (p = 0.192). Multivariate analysis confirmed that LVI was independently associated with stage progression (p = 0.006, hazard ratio = 4.00). In 85 patients who received BCG instillation, LVI was independently associated with both tumor recurrence and stage progression (p = 0.036 and 0.024, hazard ratio = 2.19 and 3.76). CONCLUSIONS: LVI is a strong indicator of an increased risk of recurrence and progression in BCG-treated patients with T1 NMIBC. This information might assist clinicians to develop appropriate management and counseling strategies for these patients.	bladder
Serum Dickkopf-1 levels as a clinical and prognostic factor in patients with bladder cancer.	Dickkopf-1 (DKK-1) is a secreted protein that inhibits Wnt signaling. However, the clinical significance and prognostic value of serum DKK-1 levels have not been previously investigated in bladder cancer in Chinese patients. Blood samples were taken from 94 consecutive patients diagnosed with bladder cancer and 60 healthy control subjects. Serum DKK-1 expression levels were measured by enzyme-linked immunosorbent assay according to the manufacturer's directions. The Kaplan-Meier method was used to estimate survival, and the log-rank test was used to test differences between the survival curves. Multivariate survival analysis was performed for all parameters deemed significant in the univariate analyses using the Cox regression model. The mean serum DKK-1 level in patients with bladder cancer was 35.91 ± 16.09 ng/mL, which was significantly higher than that in healthy individuals (9.08 ± 5.21 ng/mL, P < 0.001). Furthermore, serum DKK-1 levels were correlated significantly with lymph node metastasis (P = 0.021), distant metastasis (P = 0.013), and TNM stage (P = 0.008). Kaplan-Meier analysis using the log-rank test indicated that high serum DKK-1 levels were linked to poorer survival (33.4 vs 70.1%; P = 0.007). Multivariate analysis revealed that serum DKK-1 levels represented an independent prognostic factor for overall survival (hazard ratio = 2.365, 95% confidence interval = 1.873-8.881, P = 0.029). High serum DKK-1 levels may be associated with tumor progression and poor prognosis in bladder cancer and may be used as a potential biomarker to predict the prognosis of patients with bladder cancer.	bladder
Chemokine receptor CXCR4 and its ligand CXCL12 expressions and clinical significance in bladder cancer.	It is well known that chemokine receptors and their ligands play important roles in mediating the invasion and metastasis of malignant tumors. This aim of this study was to investigate the expression and clinical significance of chemokine receptor CXCR4 and its ligand CXCL12 in bladder tumor tissues. Cancerous and adjacent normal bladder tissues were collected from 42 patients. The expressions of CXCR4 and CXCL12 proteins were then detected by immunohistochemistry, and the expressions of CXCR4 and CXCL12 mRNAs were detected by RT-PCR. Bladder cancer tissues showed higher positive expressions of CXCR4 and CXCL12 than those in normal bladder mucosal tissues (z = 7.332, 6.758, P < 0.001). Positive expressions of CXCR4 and CXCL12 were related to the differentiation degree and invasive depth of cancer tissues (z = 2.598-4.594, P < 0.05), but not to patient gender or age (z = 0.273-0.554, P > 0.05). The expression of CXCR4 was positively correlated to CXCL12 expression in bladder cancer tissues (r = 0.661, P < 0.05). RT-PCR revealed that CXCR4 and CXCL12 mRNAs were not expressed in normal tissues. Moreover, with increased depth of invasion, CXCR4 and CXCL12 mRNA expressions gradually increased in bladder cancer tissues and showed significant intergroup differences (F = 56.642, 67.928, P < 0.01). Taken together, these results indicate that the chemokine receptor CXCR4 and its ligand CXCL12 play important roles in the occurrence and development of bladder cancer.	bladder
Clinical implications of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma.	OBJECTIVES: To characterize the site and clinical implications of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. METHODS: Patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma between 2000 and 2011 at 12 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were included in the present study. Those who underwent prior or simultaneous radical cystectomy were excluded. The site of intravesical recurrence was investigated, and the survival curves after radical nephroureterectomy were analyzed retrospectively using the Kaplan-Meier method. Multivariate analyses of factors predicting survival were carried out. RESULTS: A total of 534 patients were eligible for the present study. With a median follow up of 47 months, 205 patients (38.4%) had intravesical recurrence. The intravesical recurrence-free survival rates at 1, 2, and 5 years were 74.6%, 62.5% and 56.3%, respectively. In a subset of 137 patients with intravesical recurrence who did not have bladder cancer before or at the diagnosis of upper urinary tract urothelial carcinoma, the most frequent site of intravesical recurrence was around the cystotomy (52.6%), followed by at the posterior wall (39.4%) and at the bladder neck (35.8%). A total of 36 patients (17.6%) developed muscle-invasive bladder cancer after radical nephroureterectomy. On multivariate analyses for the subset of patients with non-muscle invasive (≤pT1) upper urinary tract urothelial carcinoma, intravesical recurrence was an independent predictor of cancer-specific survival (HR 4.27, P = 0.016) and overall survival (HR 3.00, P = 0.018). CONCLUSIONS: Most intravesical recurrences occur around the site of bladder mucosal injury within 1 year after radical nephroureterectomy, providing important insight into the mechanism of intravesical recurrence. Intravesical recurrence after radical nephroureterectomy had an impact on oncological outcomes of patients with non-muscle invasive upper urinary tract urothelial carcinoma.	bladder
MicroRNA-30a as a prognostic factor in urothelial carcinoma of bladder inhibits cellular malignancy by antagonising Notch1.	OBJECTIVE: To explore the relation between microRNA-30a (miR-30a) and Notch1, and to evaluate the potential prognostic role of miR-30a in invasive urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: In all, 50 invasive UCB tissue specimens, along with the adjacent bladder tissue specimens were obtained, and the clinical parameters of the 50 patients were analysed. Bioinformatics analysis was performed and miR-30a was selected as a potential miRNA targeting Notch1, with a luciferase assay performed to verify the binding site between miR-30a and Notch1. Quantitative real-time reverse transcriptase-polymerase chain reaction was used to assess the RNA expressions of miR-30a and Notch1, while Western Blotting and immunohistochemical staining were used to assess the protein expression of Notch1. Finally, cell proliferation, cell cycle, cell migration and invasion assays were used to evaluate the cellular effects of miR-30a and Notch1 on the UCB cell lines T24 and 5637. RESULTS: MiR-30a was downregulated in tumour tissues when compared with adjacent bladder tissues (P < 0.001), negatively correlating with Notch1 messenger RNA (R(2) 0.106, P = 0.021) in invasive UCB, and miR-30a expression further decreased in patients with shorter overall survival and disease-free survival (P = 0.039 and P = 0.037, respectively). The luciferase assay showed that miR-30a inhibited the Notch1 3'-untranslated region reporter activities in the T24 and 5637 cell lines (both P < 0.001). Both miR-30a and small interfering RNA Notch1 negatively regulated cell proliferation (P = 0.002 and P = 0.035 in T24; P = 0.029 and P = 0.037 in 5637 cell lines), activated cell cycle arrest (both P < 0.001 in T24; both P < 0.001 in 5637 cell lines), and prevented cellular migration (both P < 0.001 in T24; P = 0.003 and P < 0.001 in 5637 cell lines) and invasion (P = 0.009 and P = 0.006 in T24; P = 0.006 and P = 0.002 in 5637 cell lines) abilities. Ectopic Notch1 without the 3'untranslated region partially rescued the above-mentioned cellular effects of over-expressed miR-30a on T24 and 5637 cells. CONCLUSIONS: MiR-30a lessens cellular malignancy by antagonising oncogene Notch1 and plays an effective prognostic role in invasive UCB.	bladder
Singapore Cancer Network (SCAN) Guidelines for Neoadjuvant and Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer.	INTRODUCTION: The SCAN genitourinary cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. RESULTS: Three international guidelines were evaluated- those developed by the National Comprehensive Cancer Network (2014), the European Society of Medical Oncology (2011) and the European Association of Urology (2013). Recommendations on the use of neoadjuvant and adjuvant chemotherapy in MIBC were developed. CONCLUSION: These adapted guidelines form the SCAN Guidelines 2015 for neoadjuvant and adjuvant chemotherapy in MIBC.	bladder
Genomic complexity of urothelial bladder cancer revealed in urinary cfDNA.	Urothelial bladder cancers (UBCs) have heterogeneous clinical characteristics that are mirrored in their diverse genomic profiles. Genomic profiling of UBCs has the potential to benefit routine clinical practice by providing prognostic utility above and beyond conventional clinicopathological factors, and allowing for prediction and surveillance of treatment responses. Urinary DNAs representative of the tumour genome provide a promising resource as a liquid biopsy for non-invasive genomic profiling of UBCs. We compared the genomic profiles of urinary cellular DNA and cell-free DNA (cfDNA) from the urine with matched diagnostic formalin-fixed paraffin-embedded tumour DNAs for 23 well-characterised UBC patients. Our data show urinary DNAs to be highly representative of patient tumours, allowing for detection of recurrent clinically actionable genomic aberrations. Furthermore, a greater aberrant load (indicative of tumour genome) was observed in cfDNA over cellular DNA (P<0.001), resulting in a higher analytical sensitivity for detection of clinically actionable genomic aberrations (P<0.04) when using cfDNA. Thus, cfDNA extracted from the urine of UBC patients has a higher tumour genome burden and allows greater detection of key genomic biomarkers (90%) than cellular DNA from urine (61%) and provides a promising resource for robust whole-genome tumour profiling of UBC with potential to influence clinical decisions without invasive patient interventions.	bladder
The clinical trial on the safety and effectiveness of the photodynamic diagnosis of non-muscle-invasive bladder cancer using fluorescent light-guided cystoscopy after oral administration of 5-aminolevulinic acid (5-ALA).	OBJECTIVE: To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy. METHODS: The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0g/50mL) was performed 180-240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source. RESULTS: Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body. CONCLUSIONS: ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study.	bladder
Role of computed tomography urography in the clinical evaluation of upper tract urothelial carcinoma.	Intravenous urography has been widely used for the evaluation of upper tract urothelial carcinoma. However, computed tomography urography presently has a higher diagnostic accuracy for upper tract urothelial carcinoma (94.2-99.6%) than intravenous urography (80.8-84.9%), and has replaced intravenous urography as the first-line imaging test for investigating patients with a high risk of upper tract urothelial carcinoma. Although the detection rate for bladder tumors using standard computed tomography urography is not yet high enough to replace cystoscopy, the addition of a 60- to 80-s delayed scan after the administration of contrast material for the whole pelvis improves the detection rate. A drawback to computed tomography urography is the higher radiation dose of 15-35 mSv, compared with a mean effective dose of 5-10 mSv for intravenous urography. Among several approaches to reducing the radiation dose, the use of an iterative reconstruction algorithm is most likely to become an effective solution because of its simplicity. One advantage of computed tomography urography over intravenous urography is its ability to reliably differentiate between upper tract urothelial carcinoma and calculi or blood clots. Computed tomography urography also shows characteristic findings of other benign conditions. These findings, in combination with negative cytology, are very important diagnostic clues for avoiding an unnecessary nephroureterectomy. For the clinical staging, a recent study has reported the high diagnostic accuracy of computed tomography urography with respect to ≥pT3 tumors. The present review shows the current status of computed tomography urography for the evaluation of upper tract urothelial carcinoma.	bladder
Stapled orthotopic ileal neobladder after radical cystectomy for bladder cancer: Functional results and complications over a 20-year period.	AIMS: To present the long term-results and complications of a large series of stapled ileal orthotopic neobladders. MATERIALS AND METHODS: From 1992 to 2012 we performed 606 radical cystectomies with stapled orthotopic neobladder substitution in male patients. The median patient age was 65 years (interquartile range [IQR]: 58-71). RESULTS: Median operative time was 205 min (IQR: 180-225). The overall survival rates at 5, 10, 15, and 20 yr were 68% (336 of 494), 55% (207 of 376), 38% (98 of 259), and 23% (14 of 62), respectively, and the disease specific survival rates were 75% (371 of 494), 59% (222 of 376), 50% (130 of 259), and 35% (22 of 62), respectively. After a median follow-up of 81 months (IQR: 30-144), a total of 147 early (less than 90 days) complications (38 diversion related, 109 diversion unrelated) occurred in 144 patients (24%); 163 late complications (141 diversion related, 22 diversion unrelated) affected 141 patients (23%). At 60 months, daytime and nighttime continence was complete in 96% and 72% of cases, respectively. Urodynamic studies showed that maximum capacity, residual volume, maximum flow rate, pressure at maximum capacity, and maximum outlet closure pressure were not statistically different at 12 and 60 months postoperatively. CONCLUSIONS: The use of a stapler when performing orthotopic neobladders significantly reduces the operating time, and offers good functional results with acceptable complication rates. Our results could encourage the use of a stapler when performing an ileal neobladder during laparoscopic and robotic radical cystectomies.	bladder
Regulator of cullins-1 expression knockdown suppresses the malignant progression of muscle-invasive transitional cell carcinoma by regulating mTOR/DEPTOR pathway.	BACKGROUND: Regulator of cullins-1 (ROC1) is a key subunit in the cullin-RING ligase (CRL) protein complex. Our previous study indicated that ROC1 was essential for bladder cancer cell survival and that ROC1 knockdown inhibited CRL activity, triggering G2 phase arrest and senescence. However, the role of ROC1 in the malignant progression of bladder cancer remained unknown. METHODS: ROC1 expression in cancer cells was knocked down by siRNA silencing. The effects of ROC1 silencing were evaluated by in vitro assays for cell migration and by an in vivo mouse metastasis model. Epithelial-mesenchymal transition (EMT) induction was evaluated by immunofluorescence staining and western blotting of EMT-associated proteins. ROC1 expression in human tumours was further evaluated by immunohistochemical analysis. RESULTS: ROC1 knockdown suppresses bladder cancer cell migration by inhibiting EMT. ROC1 knockdown inhibited EMT by inhibiting mammalian target of rapamycin (mTOR) activity via the accumulation of the mTOR-inhibitory protein DEPTOR, a CRL substrate. DEPTOR knockdown partially rescued ROC1 knockdown-inhibited EMT and the ROC1-induced inhibition of cancer cell migration. Furthermore, in vivo studies using a nude mouse metastasis model confirmed the in vitro data. Finally, tissue microarray analysis of clinical bladder cancer specimens indicated a positive correlation between ROC1 expression and EMT. CONCLUSIONS: ROC1 has an important role in the malignant progression of bladder cancer via the mTOR/DEPTOR pathway. ROC1 may serve as a novel therapeutic target for the treatment of muscle-invasive transitional cell carcinoma.	bladder